Scholar Rock (SRRK) Status Update summary

Study Design and Objectives

• SRK-181, a selective TGF-beta 1 inhibitor, was evaluated with pembrolizumab in anti-PD-1 resistant advanced solid tumors in the Phase 1 DRAGON study, which included dose escalation and expansion phases.

• The study focused on safety, tolerability, and anti-tumor activity across multiple cancer types, with key endpoints including ORR, mDoR, and DCR, and incorporated biomarker analysis for patient selection.

• The recommended dose was 1500 mg every three weeks or 1000 mg every two weeks.

Safety and Tolerability

• SRK-181 was generally well tolerated with no dose-limiting toxicities or Grade 5 treatment-related adverse events; most common adverse events were dermatologic, such as rash and pruritus.

• One Grade 4 treatment-related adverse event (generalized dermatitis exfoliative) was observed; pemphigoid was the only serious adverse event ≥2%.

• Treatment-related Grade 3+ adverse events ≥5% were limited to rash.

• Dose modifications may be considered to further mitigate dermatologic adverse events, but current management strategies are effective.

Efficacy Results by Cohort

• Confirmed anti-tumor activity was observed: ORR 23.3% in ccRCC, 18.2% in HNSCC, 27.3% in melanoma (including 1 CR), and 9.1% in UC.

• Median duration of response: 7.7+ months (ccRCC), 2.2+ months (HNSCC), 4.9 months (melanoma), and 12.9 months (UC).

• Disease control rates ranged from 36.4% to 72.7% across cohorts, with responses seen in heavily pre-treated, anti-PD-1 resistant patients.

• In ccRCC, biomarker-driven selection could increase ORR to 40-50% and mDoR to 9.3-9.8 months.